Protein kinase B (PKB) is also referred to as Akt, is one of protein phosphorylases, transmits stimuli from the extracellular to the inside of a cell, and is known to be involved in response of a cell to these stimuli. In particular, it is suggested that a signal transduction from phosphatidylinositol-3 (hereinafter, referred to as PI-3) is involved in nerve cell survival, nerve regeneration or nerve differentiation. Further, a method of treating diseases such as diabetes with an inhibitor of glycogen synthase kinase-3β (hereinafter, referred to as GSK in some cases) which is one of substrates of PKB is also known. However, PKB activation and effects of treating neurodegenerative diseases such as Parkinson's disease are not necessarily confirmed in vitro. In addition, a relationship between PKB activation and effects of preventing or treating depression, anxiety, manic-depressive psychosis or PTSD (posttraumatic stress disorder; hereinafter, abbreviated as PTSD in some cases) is not confirmed.
On the other hand, as a disease in which neurodegenerative disease, that is, selective nerve cell death occurs progressively, Alzheimer's diseases, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease are known.
As current drug therapy, replacement therapy of making up for depletion of a neurotransmitter accompanied with neurodegeneration is prevailing and, regarding Parkinson's disease, a dopamine agonist such as L-dopa which is a precursor of dopamine is used as a replacement therapeutic agent or a symptomatic therapeutic agent. However, those replacement therapeutic agent and symptomatic therapeutic agent do not suppress progression of neurodegeneration, and effects are gradually lost with disease progression. For this reason, exploitation of drugs which suppress progression of neurodegeneration and promote regeneration of remaining nerve ending is desired, but drugs having such the activity have not been found out. Further, in neurodegenerative diseases, it is considered that a majority of nerve cells are degenerated at sideration, and it is thought that only degeneration suppression or promotion of regeneration of nerve ending can not regenerate sufficient function.
On the other hand, recently, great concept conversion has occurred regarding ability to regenerate a central nervous system. Previously, it has been thought that when neurodegeneration occurs in a central nervous system, recovery of function is difficult since nerve is not newly produced and replenished. However, it has been most recently and continuously revealed that a nerve stem cell and a nerve precursor cell which can newly produce a nerve are present in a central nervous system of a mature mammal including a human being, and study of possibility of regenerating disordered nerve tissue and function by activating an endogenous nerve stem cell has been initiated [see Nature Medicine, vol. 4, p. 1313-1317, 1998 and Nature Medicine, vol. 6, p. 271-277, 2000].
Benzofuran derivatives which have nerve regeneration promoting activity and are useful as a medicine for preventing or treating nerve degeneration diseases are reported in WO98/55454 and WO 00/34262.